Hatch–Waxman Reform and Accelerated Market Entry of Generic Drugs: Is Faster Necessarily Better?

Recently there has been a considerable amount of pressure to accelerate consumer access to generic drugs, which are significantly less expensive than their brand-name counterparts. One way to bring generic drugs on to the market sooner is through revision of the existing law relating to pharmaceutical patents. This iBrief describes recent regulatory changes to the Drug Price Competition and Patent Term Restoration Act (the Hatch-Waxman Act), which governs the patenting process for new drug products, as well as current legislative efforts to speed generic access through Hatch-Waxman reform. This iBrief also assesses whether these changes will be beneficial to consumers on a long-term basis

Timing of conditioned responding in a nicotine locomotor conditioning preparation: Manipulations of the temporal arrangement between context cues and drug administration

Using a locomotor conditioning preparation, we examined whether manipulating time between exposure to distinct environmental cues and nicotine administration affected conditioned responding. Rats that received nicotine (0.42 mg/kg base) immediately before placement in an environment for 30 min on eight separate occasions displayed hyperactivity relative to controls in a subsequent injection/drug-free test. This conditioned hyperactivity was weaker if nicotine was administered 15 min before environment exposure. Conditioning was not evidenced when nicotine was administered 15 min after placement or upon removal from the environment. In a follow-up experiment, rats received 45 min in the environment; nicotine was administered 15 min after placement. This group showed conditioning that was localized to the last two-thirds of a 45 min test indicating that a 15 min delay did not prevent conditioning given 30 min of environment/nicotine overlap. This apparent timing of conditioned responding was not due to increasing environment exposure to 45 min. Further, a state-dependent environmental familiarization account of locomotor hyperactivity during testing was eliminated by the finding that rats displayed temporally specific increases in activity on the test day despite the fact that the context was previously experienced without drug for 15 min on eight consecutive days

Agreement in Walking Speed Measured Using Four Different Outcome Measures: 6-Meter Walk Test, 10-Meter Walk Test, 2-Minute Walk Test, and 6-Minute Walk Test

Background: Walking speed is considered the sixth vital sign because it is a valid, reliable, and sensitive measure for assessing functional status in various populations. Purpose: The current study assessed agreement in walking speed using the 6-meter walk test, (6MWT) 10-meter walk test (10MWT), 2-minute walk test (2minWT), and 6-minute walk test (6minWT). We also determined differences in walking speed. Methods: Seventy-three healthy adults (44 females, 29 males; mean [SD] age=31.36 [10.33] years) participated. Lafayette Electronic timing devices measured walking speed for the 6MWT and 10MWT. Measuring wheels and stopwatches measured walking distance and speed for the 2minWT and 6minWT. Participants completed 1 trial, and all tests were administered simultaneously. Results: The intraclass correlation coefficient (2, 4) for the different measures of walking speed was excellent at 0.90 (95% confidence intervals, 0.86-0.93). The correlation was 0.95 between 6MWT and 10MWT, 0.94 between 2minWT and 6minWT, 0.67 between 6MWT and 2minWT, 0.63 between 10MWT and 2minWT, and 0.59 between 10MWT and 6minWT (all p \u3c 0.05). No differences in walking speed were found between the four walking tests. Conclusion: Administration of any of the four walking tests provided reliable measurement of walking speed

Improved Offshore Wind Resource Assessment in Global Climate Stabilization Scenarios

This paper introduces a technique for digesting geospatial wind-speed data into areally defined -- country-level, in this case -- wind resource supply curves. We combined gridded wind-vector data for ocean areas with bathymetry maps, country exclusive economic zones, wind turbine power curves, and other datasets and relevant parameters to build supply curves that estimate a country's offshore wind resource defined by resource quality, depth, and distance-from-shore. We include a single set of supply curves -- for a particular assumption set -- and study some implications of including it in a global energy model. We also discuss the importance of downscaling gridded wind vector data to capturing the full resource potential, especially over land areas with complex terrain. This paper includes motivation and background for a statistical downscaling methodology to account for terrain effects with a low computational burden. Finally, we use this forum to sketch a framework for building synthetic electric networks to estimate transmission accessibility of renewable resource sites in remote areas

A low energy demand scenario for meeting the 1.5 °C target and sustainable development goals without negative emission technologies

Scenarios that limit global warming to 1.5 °C describe major transformations in energy supply and ever-rising energy demand. Here, we provide a contrasting perspective by developing a narrative of future change based on observable trends that results in low energy demand. We describe and quantify changes in activity levels and energy intensity in the global North and global South for all major energy services. We project that global final energy demand by 2050 reduces to 245 EJ, around 40% lower than today, despite rises in population, income and activity. Using an integrated assessment modelling framework, we show how changes in the quantity and type of energy services drive structural change in intermediate and upstream supply sectors (energy and land use). Down-sizing the global energy system dramatically improves the feasibility of a low-carbon supply-side transformation. Our scenario meets the 1.5 °C climate target as well as many sustainable development goals, without relying on negative emission technologies

Single Tube, Multiple Enzyme Reaction for Detection of UV and Oxidative Damage in Forensic Physiological Stains

For decades, the use of DNA as a biological tool has revolutionized forensic investigations. The primary use of this genetic evidence is for identification of a victim or suspect through short tandem repeat (STR) profiling. However, the usefulness of this evidence can be compromised through inhibition of PCR, damage to the DNA, or low copy number. Here, we investigate damage induced to DNA by environmental factors. UV light is known to damage DNA by the formation of cyclobutane pyrimidine dimers, 6-4 photoproducts, and strand breaks. These lesions can stall polymerase action or misincorporate bases during extension. Oxidative damage is also common to environmentally exposed samples and can occur by microbial digestion or radiation. The primary lesion associated with oxidative damage is the formation of 8-oxoguanine, which can result in base modification. A novel assay involving a glycosylase and S1 enzymatic digestion to convert damage lesions to double strand breaks was developed to investigate damage associated with environmental exposure. Both reactions have enzyme activity in the same buffer, thus samples can be processed in the same tube to minimize the loss of DNA by transfer. Because double strand instead of single strand breaks are evaluated, samples can be evaluated on a native agarose gel which is more sensitive than damage detection techniques such as an alkaline agarose gel. Following optimization of the glycosylase plus S1 reaction, this assay was used as a tool to asses UV and oxidative damage in bloodstains exposed to the environment. The physiological stains were left uncovered to the environment for time points ranging from 1 day to 6 months. A sharp decrease in yield was observed for DNA exposed to the environment for more than 5 days. Samples exposed to environmental insults for 3 and 5 days exhibited both UV and oxidative damage as well as strand breaks. Oxidative damage was determined to constitute a higher number of damage lesions than UV damage. STR profiling revealed this damage did not result in a loss of genetic profile through 5 days of exposure. Advisor: Ashley Hal

Sensitivity of Utility-Scale Solar Deployment Projections in the SunShot Vision Study to Market and Performance Assumptions

The SunShot Vision Study explored the potential growth of solar markets if solar prices decreased by about 75% from 2010 to 2020. The ReEDS model was used to simulate utility PV and CSP deployment for this present study, based on several market and performance assumptions - electricity demand, natural gas prices, coal retirements, cost and performance of non-solar renewable technologies, PV resource variability, distributed PV deployment, and solar market supply growth - in addition to the SunShot solar price projections. This study finds that utility-scale solar deployment is highly sensitive to solar prices. Other factors can have significant impacts, particularly electricity demand and natural gas prices

Integrated Canada-U.S. Power Sector Modeling with the Regional Energy Deployment System (ReEDS)

The electric power system in North America is linked between the United States and Canada. Canada has historically been a net exporter of electricity to the United States. The extent to which this remains true will depend on the future evolution of power markets, technology deployment, and policies. To evaluate these and related questions, we modify the Regional Energy Deployment System (ReEDS) model to include an explicit representation of the grid-connected power system in Canada to the continental United States. ReEDS is unique among long-term capacity expansion models for its high spatial resolution and statistical treatment of the impact of variable renewable generation on capacity planning and dispatch. These unique traits are extended to new Canadian regions. We present example scenario results using the fully integrated Canada-U.S. version of ReEDS to demonstrate model capabilities. The newly developed, integrated Canada-U.S. ReEDS model can be used to analyze the dynamics of electricity transfers and other grid services between the two countries under different scenarios

Sensitivity of Utility-Scale Solar Deployment Projections in the SunShot Vision Study to Market and Performance Assumptions

The SunShot Vision Study explored the potential growth of solar markets if solar prices decreased by about 75% from 2010 to 2020. The ReEDS model was used to simulate utility PV and CSP deployment for this present study, based on several market and performance assumptions - electricity demand, natural gas prices, coal retirements, cost and performance of non-solar renewable technologies, PV resource variability, distributed PV deployment, and solar market supply growth - in addition to the SunShot solar price projections. This study finds that utility-scale solar deployment is highly sensitive to solar prices. Other factors can have significant impacts, particularly electricity demand and natural gas prices